Antiarrhythmic Drugs

Normal heart rate Action potential ECG

Factors precipitate arrhythmias

May includes : Ischemia, hypoxia, electrolytes disturbance, excessive catecholamines exposure , drug toxicity.

Mechanisms of arrhythmias
1- Disturbances in impulse formation.
Vagal stimulation or - receptor blocking drugs slow normal pacemaker . Acceleration of pacemaker by hypokalemia or - adrenoceptor stimulants. Development of ectopic pacemakers. -

2- Disturbances in impulse conduction

May result from block ( nodal block or bundle branch block . Reentry : circus movement In which one impulse reenters and excites areas of the heart more than ones. Some forms of reentry are anatomical in shape as in WolffParkinson White syndrome.

Antiarrhythmic Drugs
Class 1 : Na+ channel blockers Local anaesthetic effect -ve inotropic action Class 1( A ): prolongs duration of action potential & refractory period. Have K+ channel blocking effect Antimuscarinic & hypotensive effects.

. Class1(B):Shorten the duration of action potential & refractory period

Class1(C) : No effect on the duration of action or refractory period.

Class 11 : -adrenoceptor blockers. Class 111: K+ channel blockers, Prolong duration of action potential and refractory period.

 Class1V : Ca++ channel blockers. Miscellaneous drugs.

Class 1(A) Quinidine:

Cinchona plant Block open & inactivated sodium channel Block potassium channel -ve inotropic effect Antimuscarinic effect duration of action potential & refractory periods of atrium & ventricles. Hypotensive

ECG changes
Prolong Q-T interval Widening QRS complex

Phrmacokinetics
Well absorbed orally Highly bound to plasma proteins Metabolized in liver ( active metabolite) 20% excreted unchanged in urine Usually given as slow release formulation I.M. painful, I.V(marked hypotension)

Clinical uses
Atrial flutter & fibrillation it returns the rhythm back to normal sinus rhythm.
Used in treatment of ventricular arrhythmia.

Adverse effects
1- Cardiac effects A) Due to antimuscarinic effect ,in A.F.or A.F. may precipitate ventricular tachycardia B) Syncope C)Torsade de pointes D) Cardiac stand still (asystole) in patients with sick sinus syndrome .

Extracardiac adverse effects

Hypotension
Cinchonism (headache, dizziness,tinnitus,deafness ) Hypersensitivity reactions (hepatitis,thrombocytopenia) GIT, diarrhea,nausea,vomiting

Drug interactions
Quinidine increases the plasma level of digoxin by : a) displacement from tissue binding sites b) decreasing digoxin renal clearance

Procainamide
As quinidine but : Less hypotensive Less antimuscarinic Less cardiotoxic Can be given safely by I.M. or I.V. Metabolized in liver and give active metabolite which has a class 111 activity .

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Eliminated through kidney . More effective in ventricular arrhythmias , it is the second drug of choice after lidocaine in treament of ventricular arrhythmia follow acute M.I. Effective in A.F. or A.F. due to Wolff Parkinson White syndrome

Adverse effects
Systemic lupus erythematosus like syndrome. GIT : Nausea , diarrhea Torsade de pointes Hypotension

Class 1(B)
Lidocaine Shorten the duration of A.P.& R.P. Effective in ventricular arrhythmias.

Pharmacokinetics
Well absorbed after oral administration . Only 3% reach general circulation. Given only by I.V. route Excreted via kidney . Half-life 2hrs.

Therapeutic uses
First drug of choice in treatment of ventricular arrhythmias due to Acute myocardial infarction Digitalis toxicity Anaesthesia Open heart surgery

Adverse effects
Neurological effects : (contraindicated in epileptic patients ). Arrhythmias uncommon
Hypotension

Mexiletine
Effective orally Half-life (8-20hrs ). Used in chronic treatment of ventricular arrhythmias. Effective in relieving chronic pain due to diabetic neuropathy& nerve injury.

Adverse effects
Neurologic side effects

Class1(c)
Flecainide No effect on the duration of A.P.& R.P.
Proarrhythmic Approved for refractory ventricular arrhythmias.

Propafenone
Has a weak -blocking effect. Used to maintain sinus rhythm in patients with supraventricular arrhythmias including AF. Adverse effects : Metallic taste, constipation .

Class 11
Beta-Adrenoceptor-Blocking Drugs. Effective in atrial & ventricular arrhythmias that associated with Increase in sympathetic activity . Reduce the incidence of sudden arrhythmic death after myocardial infarction.

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Propranolol Metoprolol ( 1 selective) Esmolol Very short acting used for intraoperative & acute arrhythmias

Class 111
Potassium channel blockers ( Drugs that Prolong duration of action potential & refractory period ).

Sotalol
Nonselective - adrenergic receptor antagonist . Is used for the treatment of : Life- threatening ventricular arrhythmias. To maintain sinus rhythm in patients with atrial fibrillation. For treatment of supra & ventricular arrhythmias in pediatric age group.

Ibutilide
Given by a rapid I.V. infusion excreted mainly as metabolites by kidney. Used for the acute conversion of atrial flutter or atrial fibrillation to normal sinus rhythm. Q-T interval prolongation , so it precipitates torsade de pointes.

Amiodarone
A) cardiac effects
Sodium channel blocking Potassium channel blocking Calcium channel blocking - adrenoceptor blocking

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B) Extracardiac effect Peripheral vasodilation

Pharmacokinetics
Given orally Slow onset of action Long half-life(13-103 hrs ). Cumulative drug Is highly lipophilic , is concentrated in many tissues. Eliminated by liver mostly as active metabolites.

Clinical uses
Recurrent & refractory ventricular & supraventricular arrhythmias . Arrhythmias associated with Wolff Parkinson syndrome. In maintaining sinus rhythm in patients with AF.

Adverse effects
Gray- blue skin discoloration & photodermatitis . Corneal microdeposits corneal opacity ,optic neuritis, blindness pulmonary fibrosis

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hypo or hyperthyroidism Nausea & constipation Hepatic impairment neurological effects A-V block & bradycardia Hypotension

Drug interactions
Oral anticoagulant bleeding Digoxindigoxin toxicity - blockers additive effect

Class 1V
Calcium channel blockers e.g. Verapamil, Diltiazem Their main site of action is A.V.N & S.A.N. Effective only in atrial arrhythmias

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Second drugs of choice for the treatment of paroxysmal supraventricular tachycardia Not effective in Wolff Parkinson White syndrome.

Adverse effects
-Ve inotropic effect causes H.F. A-V block
Constipation , headache , peripheral edema

Miscellenous drugs
Adenosine Binds to specific G protein coupled adenosine receptors (A1&A2)opening K+ channelhyperpolarization.

influx of calcium

Pharmacokinetics & Uses

Very rapid onset of action . Short half- life (seconds) Given as a rapid I.V. bolus injection For the acute termination of re-entrant supraventricular tachycardia ( paroxysmal attack) First choice.

Adverse effects
Bronchospasm Chest pain Shortness of breath Flushing A-V block Hypotension

Contraindications
Bronchial asthma A-V block

Drug interactions
Less effective with adenosine receptor blockers ( Caffeine or theophylline
More effective with uptake inhibitors as dipyridamole

Magnesium
Used in: Digitalis induced arrhythmias Torsade de pointes Sinus tachycardia

Potassium
Used in: Digitalis induced arrhythmias